Human reproduction is inefficient with only one-fourth to one-third of fertilized human eggs likely to survive to produce a term delivery. The causes of early reproductive failures are substantially unknown, but a growing body of evidence suggests that they are a consequence of maternal exposures, including pre-conception nutrition, that may result in insults to the oocyte and periconceptual embryo. The goal of this prospective epidemiologic study is to evaluate the hypothesis that dietary patterns associated with increased oxidative stress result in delayed time-to-pregnancy or early pregnancy loss. Recently, reactive oxygen species (ROS) have been associated with spontaneous abortion, preeclampsia, and premature preterm rupture of the membranes in women and defective sperm function in men. In living cells, ROS are formed continuously as a consequence of both biochemical reactions and external factors. We propose to conduct a prospective cohort study of 575 healthy women who are planning pregnancy. The outcomes to be evaluated are time-to-pregnancy, defined as the number of menstrual cycles from the cessation of contraception to a clinically recognized pregnancy, and early, unrecognized pregnancy loss. Unrecognized pregnancy and subsequent early loss will be determined by measuring urinary human chorionic gonadotropin (hCG). Diet will be assessed prior to conception using diet records and serum assays for the antioxidant vitamins C and E, and the carotenoids. Two urinary biomarkers of oxidative stress, 8-hydroxy-2'-deoxyguanosine and F2 isoprostanes will be measured. The proposed study has a number of strengths: 1) it is large and prospective in design, with diet and oxidative stress measured prior to conception; 2) a highly sensitive and specific assay for hCG will be used to detect conceptions as early as the time of implantation; 3) dietary intake and biomarker assays of antioxidant status will be assessed at baseline and twice more during the preconception period using state-of-the-art assessment methods; 4) the proposed research has the potential to fill gaps in our understanding of the role of diet in achieving successful conception, an area where very little investigation has been done; and 5) an experienced team of scientists has been assembled. Investigators have expertise in reproductive and nutritional epidemiology, reproductive endocrinology, reproductive biology, nutrition, and nutritional biochemistry. Reproductive failure is a serious public health concern. The inability to have children carries significant personal, societal, and financial consequences. The steps to diagnose and treat infertility are time- consuming, invasive, and often stressful for the couple. In the US, an estimated 6.2 million women are currently infertile, with projections that there will be 7.7 million infertile women by the year 2025. Very little is known about the role of diet or dietary components in achieving conception and maintaining very early pregnancy. [unreadable] [unreadable] [unreadable]